Gene-Environment Interaction: Small Deletions (DELs) and Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) and Potential Implications for Therapy.
Farzana Jasmine, Armando Almazan, Yuliia Khamkevych, Maria Argos, Mohammad Shahriar, Tariqul Islam, Christopher R Shea, Habibul Ahsan, Muhammad G Kibriya
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引用次数: 0
Abstract
Arsenic (As) is a risk factor for non-melanoma skin cancer (NMSC). From a six-year follow-up study on 7000 adults exposed to As, we reported the associations of single-nucleotide variation in tumor tissue and gene expression. Here, we identify the associations of small deletions (DELs) and transcriptomic profiles in NMSC. Comparing the (a) NMSC tissue (n = 32) and corresponding blood samples from each patient, and (b) an independent set of non-lesional, healthy skin (n = 16) and paired blood, we identified NMSC-associated DELs. Differential expressions of certain gene pathways (TGF-β signaling pathway, IL-17 pathway, PD-L1 pathway, etc.) showed significant interactions with these somatic DELs and As exposure. In low-As-exposure cases, the DELs in APC were associated with the up-regulation of inflamed T-Cell-associated genes by a fold change (FC) of 8.9 (95% CI 4.5-17.6), compared to 5.7 (95% CI 2.9-10.8) without APC DELs; in high-As-exposure cases, the APC DELs were associated with an FC of 5.8 (95% CI 3.5-9.8) compared to 1.2 (95% CI -1.3 to 1.8) without APC DELs. We report, for the first time, the significant associations of somatic DELs (many in STR regions) in NMSC tissue and As exposure with many dysregulated gene pathways. These findings may help in selecting groups of patients for potential targeted therapy like PD-L1 inhibitors, IL-17 inhibitors, and TGF-β inhibitors in the future.
CellsBiochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
9.90
自引率
5.00%
发文量
3472
审稿时长
16 days
期刊介绍:
Cells (ISSN 2073-4409) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to cell biology, molecular biology and biophysics. It publishes reviews, research articles, communications and technical notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided.